Iron deficiency (ID) is the most common and widespread nutritional disorder worldwide with over 2 billion people suffering significant negative health effects. There is a widespread, serious misperception that oral iron supplements are safe and effective at alleviating ID; yet in a recent Cochrane review of 67 clinical trials, women taking oral iron supplements had just a 38% decreased risk of ID at the end of treatment compared to placebo. Moreover, these subjects had a 114% increased risk of side effects, the vast majority of which were associated with gastrointestinal (GI) disturbance. The current standard of care for treating ID involves iron salts or more recently iron nanoparticles which are degraded in the stomach and release elemental iron. SideroBiosciences has developed a disruptive technology consisting of nutritional yeast modified to express a H-ferritin:iron complex known as BioFe. The concept of using an H- ferritin;iron complex is rooted in mimicking iron delivery from breast milk and using nutritional yeast provides an easily accessible and economical platform for marketing and consumption by many different cultures and age groups. That the ferritin:iron complex in BioFe is specifically H- ferritin distinguishes it from L-ferritin or plant ferritin, both of which have had limited success as iron supplements because they are degraded in the gut to release the iron and thus use the same pathway into enterocytes as iron salts and thus their performance is at best similar to the iron salts. BioFe has been successfully tested in rodents, non-human primates and humans (including a STTR funded study). While the absorption and secretion of elemental iron across the membranes of intestinal enterocytes are relatively well described, the receptor(s), transporter(s), and regulatory mechanism(s) for H-Ferritin:Iron complexes have not been described. In multiple discussions with potential marketing partners, SideroBiosciences has been consistently queried for more details on how the entry of the ferritin;iron complex into the body are different from iron salts. Therefore,to address these questions, we have provided exciting pilot data to pursue in this application that will interrogate mechanisms by which Ferritin:Iron complexes are transported across the apical membrane of intestinal enterocytes, processed within the intestinal cells, and secreted across the basolateral membrane into the systemic circulation. Furthermore, because the mechanism of release from the enterocyte is different from elemental iron BioFe will be tested for its ability to treat inflammatory mediated iron deficiency in rodents to position itself to be clinically tested in individuals with ID resulting from chronic inflammation which is a significant clinical problem that BioFe can address.